Novel deletion of SPAST in a Chinese family with hereditary spastic paraplegia

Feng, Yimin; Ke, Xin; Zhai, Meng; Xin, Qian; Gong, Yaoqin; Liu, Qiji

doi:10.11622/smedj.2013102

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…To date, there has been no systematic genetic and clinical analysis of a large cohort of AD-HSPs in China and only several SPG4 families [10,11,12,13], a few SPG3 families [14,15,16,17]and 3 SPG6 families [17,18 have been] reported. Lin et al [19] mapped the causative gene for an AD-HSP family to 3q24-q26 and revealed that it was caused by a missense mutation in the gene for the acetyl-CoA transporter (SLC33A1) .…”

Section: Introductionmentioning

confidence: 99%

Mutation and Clinical Characteristics of Autosomal-Dominant Hereditary Spastic Paraplegias in China

Luo¹,

Chen²,

Zhan³

et al. 2014

Neurodegener Dis

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Background: Hereditary spastic paraplegias constitute a heterogeneous group of inherited neurodegenerative disorders. To date, there has been no systematic mutation and clinical analysis for a large group of autosomal-dominant hereditary spastic paraplegias in China. Objective: The purpose of this study was to investigate the mutation frequencies and the clinical phenotypes of Chinese spastic paraplegia patients. Methods: Direct sequencing and a multiplex ligation-dependent probe amplification assay were applied to detect the mutations of SPAST and ATL1 in 54 autosomal-dominant hereditary spastic paraplegia probands and 66 isolated cases. Next, mutations in NIPA1, KIF5A, REEP1 and SLC33A1 were detected in the negative patients. Subsets of spastic paraplegia patients were genotyped for the modifying variants. Further, detailed clinical data regarding the genetically diagnosed families were analysed. Results: Altogether, 27 families were diagnosed as SPG4, 3 as SPG3A and 1 as SPG6. No mutations in KIF5A, REEP1 or SLC33A1 were found; 9 SPAST mutations were novel. There was no p.S44L or p.P45Q variant in SPAST and no p.G563A variant in HSPD1 in either the 120 spastic paraplegia patients or the 500 controls. There was a remarkable clinical difference between the SPG4 and non-SPG4 patients and even between genders among the SPG4 patients. Non-penetrance and remarkable gender difference were observed in some SPG4 and SPG3A families. Conclusions: Our data confirm that hereditary spastic paraplegias in China represent a heterogeneous group of genetic neurodegenerative disorders in autosomal-dominant and apparently sporadic forms. Novel genotype-phenotype correlations were established.

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Section: Introductionmentioning

confidence: 99%

Mutation and Clinical Characteristics of Autosomal-Dominant Hereditary Spastic Paraplegias in China

Luo¹,

Chen²,

Zhan³

et al. 2014

Neurodegener Dis

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“…The SPAST gene, also known as the SPG4 gene, has been mapped to chromosome 2p21-p22, and encodes spastin, an amino acid protein belonging to the broad AAA (triple A; ATPase associated with various cellular activities) family (16). With two initiation codons, SPG4 mRNA synthesizes two spastin isoforms, a 616-amino acid (68 kDa) isoform called M1 and a 530-amino acid (60 kDa) isoform called M87.…”

Section: Discussionmentioning

confidence: 99%

“…(5,14), and variants in SPG5, SPG11, and SPG15 have been described as the most frequent causes for AR-HSP (15) . SPG4 as the commonest AD HSP form in many population, although de novo variations do appear, most SPAST-HSP cases are hereditary (16)(17)(18). It has been reported that the average onset of AD in SPG4/SPAST patients was 24.79 (95% CI: 21.00-28.58) (19) or mostly in their fourth decade (20).…”

Section: Introductionmentioning

confidence: 99%

A novel variant of SPAST in a pedigree with pure hereditary spastic paraplegia in Yunnan Province

Shen¹,

Zhang²,

Li³

et al. 2022

Ann Transl Med

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Background: Hereditary spastic paraplegia (HSP) is a rare group of genetically heterogeneous, neurodegenerative disorders. The aim of this study was to identify pathological candidate genes and variants in a large pedigree cohort of 11 purely HSP patients in Yunnan Province.Methods: Whole-exome sequencing (WES) was applied to 2 HSP patients and 1 control patient to screen out the candidate gene variants. Then, filtration and verification of these pathological variants were performed by Sanger sequencing.Results: After the raw data were filtered, two genes with novel variations (SPAST: c.1510 C>T, p.Gln504X, RefSeq.NM_199436; DNAJC16: c.718 C>T, p.Q240X, Ref Seq NM_015291) were identified. The accession numbers of the genes in the ClinVar database were SCV001573094 and SCV001573804, respectively. One gene with a reported single nucleotide polymorphism (CPT1C: rs150853576) was filtered as a candidate variant. Using Sanger sequencing, the novel SPAST gene (protein: Spastin) variant leading to a predicted premature termination and an 18% deletion of the SPAST/spastic paraplegia type 4 (SPG4) protein was confirmed to exist only in affected individuals. The candidate CPT1C and DNAJC16 variants were verified in almost all HSP patients, with one exception.Conclusions: Considering that the clinical symptoms and time of onset of HSP are highly heterogeneous, the SPAST as a genotype-phenotype cosegregated variant might be the causative gene of this pedigree, and the other two variants might present cumulative risks to the occurrence and progression of HSP. These three candidate genes with or without novel variants may be potential contributors to disease onset, and therefore useful diagnostic and therapeutic biomarkers. Further research is required to confirm the functions of these genes.

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“…Já as mutações missenses são menos comuns (29%). Poucos polimorfismos foram descritos, refletindo a natureza conservada desta proteína entre as espécies [56][57][58][59][60][61][62][63][64][65][66][67][68][69][70] .…”

Section: Spg4 -Espastinaunclassified

Estudo genético-molecular de pacientes discordantes de Paraplegia Espástica Hereditária do tipo 4

Cavaçana¹

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Novel deletion of SPAST in a Chinese family with hereditary spastic paraplegia

Cited by 5 publications

References 23 publications

Mutation and Clinical Characteristics of Autosomal-Dominant Hereditary Spastic Paraplegias in China

Mutation and Clinical Characteristics of Autosomal-Dominant Hereditary Spastic Paraplegias in China

A novel variant of SPAST in a pedigree with pure hereditary spastic paraplegia in Yunnan Province

Estudo genético-molecular de pacientes discordantes de Paraplegia Espástica Hereditária do tipo 4

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